Schizophrenia is a syndrome which encompasses a variety of mental symptoms like auditory hallucinations, paranoia, delusions, catatonia, bizarre behavior and emotional withdrawal. Schizophrenia affects about 1% of the total population and its economical as well as social burden on society are enormous. The onset of the disease occurs in early age and, thus, patients typically need life-long medical and psychiatric supervision. Schizophrenia is, therefore, rated as one of the most costly diseases in the industrial world (Carpenter, et al., 1994).
No common parameter associated with schizophrenia has been identified and, therefore, the internationally agreed diagnosis of this disease is still based today solely on psychiatric evaluation. Known risk factors associated with schizophrenia, are genetic predisposition, birth during winter and complications during pregnancy or birth. Viral and/or bacterial infections with a subsequent autoimmune reaction have been proposed as causative factors for the increasing outbreak of schizophrenia (DeLisi, et al, 1987).
Schizophrenia has been shown to involve an autoimmune process and lately autoantibodies and cytotoxic T-cells against platelets were demonstrated in schizophrenic patients (Shinitzky, 1991, Deckmann, 1996, Shinitzky, 1999, U.S. Pat. No. 6,008,001). The cytotoxic T-cell reaction in schizophrenic patients was evaluated by a skin test in which most schizophrenic patients reacted positively against their autologous platelets whereas only a very minor number of non-schizophrenic tested individuals reacted positively in this test (Shinitzky, 1999, WO 99/30163).
In addition elevated levels of autoantibodies against platelets were observed in schizophrenic patients but not in patients suffering from manic-depressive disorder, depression, personality disorders and schizoaffective disorder (Shinitzky, 1991 and Deckmann, 1996).
In the inventors' prior work several proteins which bind autoantibodies that are found in elevated levels in body fluids of schizophrenic patients were identified (Shinitzky et al, 1999, WO 99/51725). These proteins reacted with purified platelet derived autoantibodies (PAA) from schizophrenic patients but could not differentiate between plasma or blood samples of schizophrenic and non-schizophrenic individuals. Enzymatic digestion of one of these proteins, the enzyme Enolase, resulted in a fragment which bound to plasma samples of schizophrenic patients substantially higher than it bound to plasma samples of non-schizophrenic individuals. On the basis of this fragment several additional peptides were synthesized and such having a high binding activity to PAAs of schizophrenic individuals were isolated. The structure of the antigenic epitope of these peptides was found to be a three-dimensional epitope which, by using a computerized program was predicted to be a cyclic structure comprising a hydrophobic core and an extension having about two positive charges. Immunological studies demonstrated that only the oxidized cyclic form of the peptide was reactive with the anti-platelet autoantibodies. These synthesized peptides comprised at least 17 amino acids (a.a.).